Département de médecine, Université de Montréal, Montréal, QC, Canada.
Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, Montréal, QC, Canada.
Front Immunol. 2022 Jun 30;13:907591. doi: 10.3389/fimmu.2022.907591. eCollection 2022.
Immune checkpoint inhibitors (ICI) are being increasingly used to successfully treat several types of cancer. However, due to their mode of action, these treatments are associated with several immune-related adverse events (irAEs), including immune-mediated autoimmune-like hepatitis in 5 to 10% of cases. The specific immune mechanism responsible for the development of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI) is currently unknown. This review summarizes the current knowledge on hepatic irAEs during cancer immunotherapy. It also addresses the clinical management of ILICI and how it is becoming an increasingly important clinical issue. Clinical, histological, and laboratory features of autoimmune hepatitis (AIH) and ILICI are compared, and their shared and distinctive traits are discussed in an effort to better understand the development of hepatic irAEs. Finally, based on the current knowledge of liver immunology and AIH pathogenesis, we propose a series of events that could trigger the observed liver injury in ICI-treated patients. This model could be useful in the design of future studies aiming to identify the specific immune mechanism(s) at play in ILICI and improve immune checkpoint inhibitor cancer immunotherapy.
免疫检查点抑制剂（ICI）被越来越多地用于成功治疗多种类型的癌症。然而，由于其作用模式，这些治疗与几种免疫相关的不良反应（irAE）相关，包括在 5%至 10%的病例中发生的免疫介导的自身免疫样肝炎。目前尚不清楚导致免疫检查点抑制剂（ILICI）引起的免疫介导性肝损伤的特定免疫机制。这篇综述总结了癌症免疫治疗期间肝 irAE 的现有知识。它还讨论了 ILICI 的临床管理以及它如何成为一个越来越重要的临床问题。比较了自身免疫性肝炎（AIH）和 ILICI 的临床、组织学和实验室特征，并讨论了它们的共同和独特特征，以努力更好地了解肝 irAE 的发展。最后，根据目前对肝脏免疫学和 AIH 发病机制的了解，我们提出了一系列可能导致在接受 ICI 治疗的患者中观察到的肝损伤的事件。该模型可用于设计旨在确定 ILICI 中发挥作用的特定免疫机制并改善免疫检查点抑制剂癌症免疫治疗的未来研究。
